Comparative study on effects of pentoxifylline, prednisolone and colchicine in experimental alveolitis

Entzian, P.; Zähringer, Ulrich; Schlaak, M; Gerlach, Christiane; Galle, J.; Zabel, P.

doi:10.1016/s0192-0561(98)00056-3

Cited by 22 publications

(8 citation statements)

References 26 publications

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“…The significance of inflammation in the pathogenesis of IPF has been questioned, in part because of the therapeutic failure of glucocorticoids (Chapman 2004). However, our findings in mice and those of others in both mice (Tamagawa et al 2000) and rats (Nettelbladt et al 1990;Entzian et al 1998;) suggest that the pattern of inflammation in fibrosis may be glucocorticoid resistant, as it is in some other remodeling diseases such as chronic obstructive pulmonary disease. In contrast, in airway wall remodeling induced by chronic antigen exposure, glucocorticoid treatment reduces TGF-b, collagen, and myofibroblast accumulation in a form of inflammation that is well established as being glucocorticoid responsive (Miller et al 2006).…”

Section: Figmentioning

confidence: 57%

“…Nettelbladt and coworkers found no effect of MP treatment on bleomycininduced lung oedema or BAL inflammatory cell infiltration in a rat model (Nettelbladt et al 1990). Similarly, prednisolone treatment was found to have little effect on either bleomycin-induced BAL neutrophilia or fibrosis in rats (Entzian et al 1998). …”

Section: Figmentioning

confidence: 99%

“…The majority of these studies suggest that glucocorticoids have antiinflammatory and antifibrotic activity in the bleomycin model (Hagimoto et al 1997;Phan et al 1981); (Dik et al 2003a(Dik et al , 2003b). This has not been a universal finding, as several studies have found that glucocorticoids have no beneficial effects (Entzian et al 1998;Nettelbladt et al 1990;Tamagawa et al 2000).…”

Section: Introductionmentioning

confidence: 99%

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Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in miceThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Langenbach

Wheaton

Fernandes

et al. 2007

Can. J. Physiol. Pharmacol.

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Bleomycin-induced lung fibrosis in mice reproduces some key features of pulmonary fibrosis in humans including alveolar inflammation, myofibroblast proliferation, and collagen deposition. Glucocorticoids have been used as first-line therapy for the treatment of lung fibrosis, although their clinical efficacy is equivocal. We examined the effect of the glucocorticoid, methylprednisolone (MP), and the estrogen metabolite, 2-methoxyestradiol (2MEO) on bleomycin-induced bronchoalveolar inflammation, fibrosis, and changes in lung function. The characterization of the time-course of the bleomycin-induced fibrosis indicated that lung dry mass and hydroxyproline content showed less variance than histopathological assessment of fibrosis. The bleomycin-induced increases in bronchoalveolar lavage (BAL) fluid cell number and protein levels were not significantly influenced by treatment with either MP (1 mg.(kg body mass)(-1).day(-1), i.p.) or 2MEO (50 mg.(kg body mass)(-1).day(-1), i.p.). Lung fibrosis, measured histopathologically or by hydroxyproline content, was not significantly influenced by either MP or 2MEO treatment, whereas the latter agent did reduce the increment in lung dry mass. The enlargement of alveolar airspaces and the decline in lung compliance were exacerbated by MP treatment. These data suggest that bleomycin-induced pulmonary fibrosis is resistant to inhibition by concurrent treatment with either glucocorticoids or 2MEO.

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Section: Figmentioning

confidence: 57%

Section: Figmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in miceThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Langenbach

Wheaton

Fernandes

et al. 2007

Can. J. Physiol. Pharmacol.

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“…), Immunosuppressants (Cyclosporin-A (Lossos, Or, Goldstein, Conner, & Breuer, 1996), Rapamycin analogue SDZ RAD (Simler et al, 2002)), Corticosteroids (Dexamethasone (F. Chen et al, 2006;Dik et al, 2003;H. P. Li, Li, He, Yi, & Kaplan, 2004), Methylprednisolone (Phan, Thrall, & Williams, 1981), Prednisolone (Chaudhary, Schnapp, & Park, 2006;Entzian et al, 1998) 1986) etc. ), and Pirfenidone (Ammar et al, 2006;Gurujeyalakshmi, Hollinger, & Giri, 1999;Iyer, Gurujeyalakshmi, & Giri, 1999;Iyer, Hyde, & Giri, 2000;Iyer, Margolin, Hyde, & Giri, 1998;Iyer et al, 1995;Kakugawa et al, 2004;Mansoor, Chen, Schelegle, & Giri, 1999;Schelegle, Mansoor, & Giri, 1997).…”

Section: Drug Intervention Studies In the Bleomycin Modelmentioning

confidence: 99%

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Moeller

Ask

Warburton

et al. 2008

The International Journal of Biochemistry & Cell Biology

821

724

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Different animal models of pulmonary fibrosis have been developed to investigate potential therapies for idiopathic pulmonary fibrosis (IPF). The most common is the bleomycin model in rodents (mouse, rat and hamster). Over the years, numerous agents have been shown to inhibit fibrosis in this model. However, to date none of these compounds are used in the clinical management of IPF and none has shown a comparable antifibrotic effect in humans. We performed a systematic review of publications on drug efficacy studies in the bleomycin model to evaluate the value of this model regarding transferability to clinical use. Between 1980 and 2006 we identified 246 experimental studies describing beneficial antifibrotic compounds in the bleomycin model. In 221 of the studies we found enough details about the timing of drug application to allow inter-study comparison. 211 of those used a preventive regimen (drug given ≤ day 7 after last bleomycin application), only 10 were therapeutic trials (> 7 days after last bleomycin application). It is critical to distinguish between drugs interfering with the inflammatory and early fibrogenic response from those preventing progression of fibrosis, the latter likely much more meaningful for clinical application. All potential antifibrotic compounds should be evaluated in the phase of established fibrosis rather than in the early period of bleomycin-induced inflammation for assessment of its antifibrotic properties. Further care should be taken in extrapolation of drugs successfully tested in the bleomycin model due to partial reversibility of bleomycin induced fibrosis over time. The use of alternative and more robust animal models, which better reflect human IPF, is warranted.

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“…No randomized placebo-controlled trials have ever been conducted evaluating the efficacy of corticosteroids in IPF. However, the existing data in humans are disappointing [114], as they are in animal models of pulmonary fibrosis [115,116]. Such negative data may reflect the indiscriminate inhibition by corticosteroids of both profibrotic (e.g.…”

Section: Corticosteroidsmentioning

confidence: 99%

Eicosanoids: mediators and therapeutic targets in fibrotic lung disease

Charbeneau

Peters‐Golden

2005

Clinical Science

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Fibrosis is a common end-stage sequella of a number of acute and chronic lung diseases. Current concepts of pathogenesis implicate dysregulated interactions between epithelial cells and mesenchymal cells. Although investigative efforts have documented important roles for cytokines and growth factors in the pathogenesis of fibrotic lung diseases, these observations have not as yet been translated into efficacious therapies, and there is a pressing need for new pathogenetic insights and therapeutic approaches for these devastating disorders. Eicosanoids are lipid mediators derived from arachidonic acid, the most studied of which are the prostaglandins and leukotrienes. Although they are primarily known for their roles in asthma, pain, fever and vascular responses, present evidence indicates that eicosanoids exert relevant effects on immune/inflammatory, as well as structural, cells pertinent to fibrogenesis. In general, leukotrienes promote, whereas prostaglandin E(2) opposes, fibrogenic responses. An imbalance of eicosanoids also exists in pulmonary fibrosis, which favours the production of leukotrienes over prostaglandin E(2). This review highlights the role of this imbalance in the evolution of fibrotic lung disease, discusses the mechanisms by which it may arise and considers approaches for therapeutic targeting of eicosanoids in these conditions.

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Comparative study on effects of pentoxifylline, prednisolone and colchicine in experimental alveolitis

Cited by 22 publications

References 26 publications

Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in miceThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

Resistance of fibrogenic responses to glucocorticoid and 2-methoxyestradiol in bleomycin-induced lung fibrosis in miceThis article is one of a selection of papers published in the Special Issue on Recent Advances in Asthma Research.

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Eicosanoids: mediators and therapeutic targets in fibrotic lung disease

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